The human serological response to several envelope-associated proteins and adenylate cyclase toxin of B. pertussis was examined using immunoblot techniques. Antigens recognized by sera from individuals with culture-confirmed pertussis as well as by sera from infants immunized with three doses of conventional whole-cell pertussis vaccine included a 63,000 Da protein that was shown to be antigenically related to a mycobacterial heat-shock protein and structurally related to the chaperonin family of proteins involved in protein folding and assembly. B. pertussis lipooligosaccharide was also recognized by antibodies in certain of these sera. A 29,000 Da species reacted with sera from convalescent individuals whereas a 91,000 Da species reacted with sera from vaccinated individuals. Antibodies to adenylate cyclase toxin were common in sera from individuals diagnosed with pertussis, however these antibodies were rarely found in children who had received three doses of DTP vaccine. Sera from neonates (cord blood) and corresponding maternal sera were examined for antibodies to Bordetella adenylate cyclase. Similar levels of antigen specific antibodies (IgG isotype) were found in each serum sample of a given neonate-maternal pair suggesting that antibodies to adenylate cyclase are passively transferred through the placenta. These antibodies may have been elicited by previous exposure of the mothers to B. pertussis or by vaccination of the mother with pertussis vaccine since all four pertussis vaccines currently in use in the US were capable of eliciting in mice antibodies reactive with adenylate cyclase. Alternatively, these antibodies may have been elicited by exposure of mothers to cross-reactive antigens such as E. coli a-hemolysin since all of the neonatal sera contained antibodies reactive with this antigen. Antibodies to adenylate cyclase have been previously shown to passively protect mice against challenge with B. pertussis. Therefore the possibility exists that these antibodies may help protect the newborn child against pertussis.